Colloid Solutions for Fluid Resuscitation in Patients with Sepsis: Systematic Review of Randomized Controlled Trials

Abstract

Background

Colloids are widely used for fluid resuscitation in patients with sepsis. But the optimal type of fluid remains unclear.

Objective

Our aim was to assess the effects on mortality and safety of different colloid solutions in patients with sepsis requiring volume replacement by examining direct comparisons of colloid solutions.

Methods

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, China Biological Medicine Database, VIP Chinese Journals Database, and CNKI China National Knowledge Infrastructure Whole Article Database. Randomized clinical trials comparing different colloids in septic patients needing fluid resuscitation were selected.

Results

Seventeen randomized clinical trials with a total 1281 participants met the inclusion criteria. Mortality was obtained in all trials. For intervention of albumin vs. hydroxyethyl starch solution (HES), the relative risk (RR) of death was 0.98 (95% confidence interval [CI] 0.74−1.30). For intervention of albumin vs. gelatin, the RR of death was 2.4 (95% CI 0.31−18.35). For intervention of gelatin vs. HES, the RR of death was 1.02 (95% CI 0.79−1.32). For the intervention of HES vs. dextran, the RR of death was 1.38 (95% CI 0.28−6.78). For the intervention of gelatin vs. dextran, RR of death was not estimable. For albumin vs. dextran, no trial was included. Four trials of intervention of albumin vs. HES recorded the change of severity score.

Conclusions

There is no evidence that one colloid solution is more effective and safer than another for fluid resuscitation in sepsis. The severity score is improved in HES, but the confidence intervals are wide.

Introduction

Sepsis is a systemic illness caused by a known or suspected microbial invasion of normally sterile parts of the body. It is a term that specifically serves to distinguish an illness of microbial origin from an identical clinical syndrome that can arise in several nonmicrobial conditions. Severe sepsis is accompanied by organ dysfunction or hypoperfusion or hypotension. Finally, when severe sepsis is accompanied by hypotension or need for vasopressors despite adequate fluid resuscitation, it turns into septic shock (1). Sepsis is considered as the leading cause of death in noncoronary intensive care units (ICUs) (2). In the United States, a large epidemiological study of up to 6 million people gave an incidence of 3 per 1000 population per year, or about 750,000 cases a year. Mortality was 28.6% or 215,000 deaths nationally. The average cost per case was $22,100, with annual total costs of $16.7 billion nationally. The incidence of sepsis and the number of sepsis-related deaths is increasing 3, 4, 5.

Fluid resuscitation has been shown to improve survival for patients presenting with septic shock in a randomized, controlled, single-center study (6). Microcirculatory dysfunction is a pivotal element of the pathogenesis of severe sepsis and septic shock (7). Misdistribution of fluid in the microcirculation is typical of septic shock that is caused by endotoxin-induced endothelial damage (8). Colloids contain particles that are large enough to gain an oncotic pressure across the microvascular membrane. Compared with crystalloids, they have greater intravascular persistence. They are able to correct volume loss rapidly, improve blood flow, and have a long duration of their effect (9). The pharmacological and pharmacodynamic properties of the various colloids differ widely (10). International guidelines suggest infusion of either natural or artificial colloids or crystalloids (11). No evidence supported the effectiveness of one type of fluid solution over another (12). However, as the volume of distribution is much larger for crystalloids than for colloids, resuscitation with crystalloids alone requires more fluid and results in more edema, and might be inferior to combination therapy with colloids (11). Colloid solutions combined with crystalloids are widely used for replacement of fluid volume, particularly in Europe (9).

These solutions can be natural colloid (e.g., human albumin, plasma protein fraction) or synthetic colloid (e.g., dextrans, hydroxyethyl starch solution [HES], and gelatin) (13). However, it is still uncertain which colloid is the best in sepsis. The duration of intravascular persistence of colloids depends on molecular size, shape, ionic charge, and the porosity of the capillary endothelium (10). Albumin is the colloid containing particles of consistent molecular weight (monodisperse). The other colloids are polymers and contain particles with a wide range of molecular weights (14). This can make colloids vary in their safety and effectiveness. Compared with other colloidal solutions, human albumin solutions are expensive and limited in availability. Dextrans seems to have the most unfavorable risk-to-benefit ratio among the currently available synthetic colloids due to their relevant anaphylactoid potentialities, risk of renal failure, and, particularly, their major impact on hemostasis. The effects of gelatin on kidney function are currently unclear, but potential disadvantages of gelatin include high anaphylactoid potentialities and a limited volume effect compared with dextrans and HES (15). Modern HES preparations have the lowest risk of anaphylactic reactions among the synthetic colloids. Older HES preparations have repeatedly been reported to impair renal function and hemostasis 16, 17. There have been previous systematic reviews suggesting that no one colloid solution is more effective or safer than any other colloids for fluid resuscitation in patients who need volume replacement (13). Sepsis is one of the diseases associated with hypovolemia or hypoperfusion, which is different from other diseases (such as bleeding and capillary leakage) on pathophysiological mechanism. Consequently, to quantify the effect on mortality and the safety of different colloids in the management of critically ill patients with sepsis, we conducted this systematic review to identify and synthesize all available evidence.